Intraoperative Evaluation of Breast Tissues During Breast Cancer Operations Using the MasSpec Pen.

Importance: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance. Objective: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information. Design, Setting, and Participants: In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult patients undergoing breast surgery for ductal carcinomas or nonmalignant conditions. Fresh-frozen tissue samples and touch imprints were analyzed in a laboratory. Intraoperative in vivo and ex vivo breast tissue analyses were performed by surgical staff in operating rooms (ORs) within 2 different hospitals at the Texas Medical Center. Molecular data were used to build statistical classifiers. Main Outcomes and Measures: Prediction results of tissue analyses from classification models were compared with gross assessment, frozen section analysis, and/or final postoperative pathology to assess accuracy. Results: All data acquired from the 143 banked tissue samples, including 79 healthy breast and 64 IDC tissues, were included in the statistical analysis. Data presented rich molecular profiles of healthy and IDC banked tissue samples, with significant changes in relative abundances observed for several metabolic species. Statistical classifiers yielded accuracies of 95.6%, 95.5%, and 90.6% for training, validation, and independent test sets, respectively. A total of 25 participants enrolled in the clinical, intraoperative study; all were female, and the median age was 58 years (IQR, 44-66 years). Intraoperative testing of the technology was successfully performed by surgical staff during 25 breast operations. Of 273 intraoperative analyses performed during 25 surgical cases, 147 analyses from 22 cases were subjected to statistical classification. Testing of the classifiers on 147 intraoperative mass spectra yielded 95.9% agreement with postoperative pathology results. Conclusions and Relevance: The findings of this diagnostic study suggest that the mass spectrometry-based system could be clinically valuable to surgeons and patients by enabling fast molecular-based intraoperative assessment of in vivo and ex vivo breast tissue samples and surgical margins.

Multicenter Study Using Desorption-Electrospray-Ionization-Mass-Spectrometry Imaging for Breast-Cancer Diagnosis.

The histological and molecular subtypes of breast cancer demand distinct therapeutic approaches. Invasive ductal carcinoma (IDC) is subtyped according to estrogen-receptor (ER), progesterone-receptor (PR), and HER2 status, among other markers. Desorption-electrospray-ionization-mass-spectrometry imaging (DESI-MSI) is an ambient-ionization MS technique that has been previously used to diagnose IDC. Aiming to investigate the robustness of ambient-ionization MS for IDC diagnosis and subtyping over diverse patient populations and interlaboratory use, we report a multicenter study using DESI-MSI to analyze samples from 103 patients independently analyzed in the United States and Brazil. The lipid profiles of IDC and normal breast tissues were consistent across different patient races and were unrelated to country of sample collection. Similar experimental parameters used in both laboratories yielded consistent mass-spectral data in mass-to-charge ratios ( m/ z) above 700, where complex lipids are observed. Statistical classifiers built using data acquired in the United States yielded 97.6% sensitivity, 96.7% specificity, and 97.6% accuracy for cancer diagnosis. Equivalent performance was observed for the intralaboratory validation set (99.2% accuracy) and, most remarkably, for the interlaboratory validation set independently acquired in Brazil (95.3% accuracy). Separate classification models built for ER and PR statuses as well as the status of their combined hormone receptor (HR) provided predictive accuracies (>89.0%), although low classification accuracies were achieved for HER2 status. Altogether, our multicenter study demonstrates that DESI-MSI is a robust and reproducible technology for rapid breast-cancer-tissue diagnosis and therefore is of value for clinical use.

Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging.

Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. Graphical Abstract Desorption electrospray ionization mass spectrometry imaging is used to differentiate metastatic cancer from adjacent lymph node tissue.

Operative and Oncologic Outcomes in 9861 Patients with Operable Breast Cancer: Single-Institution Analysis of Breast Conservation with Oncoplastic Reconstruction.

BACKGROUND: Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer. METHODS: This retrospective cohort study interrogated a single institution's prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed. RESULTS: There were 10,607 operations performed for 9861 patients. Median follow-up was 3.4 years (range, 0-9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R. CONCLUSIONS: Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM.

Identifying risk factors for surgical site complications after laparoscopic ventral hernia repair: evaluation of the Ventral Hernia Working Group grading system.

BACKGROUND: In 2010, the Ventral Hernia Working Group (VHWG) published a grading system to assess the risk of surgical site complications in patients undergoing ventral hernia repair. This study evaluated the predictive value of the VHWG classification for the surgical outcomes of laparoscopic ventral hernia repair (LVHR) and identified independent factors associated with surgical site infection (SSI) and surgical site occurrence (SSO). METHODS: A retrospective review was performed of all patients who underwent LVHR over a 10-year period at two institutions. The U.S. Centers for Disease Control and Prevention definition of SSI and the VHWG definition of SSO were used. Univariable analysis was performed using the Student t-test, analysis of variance, chi-square test, or Fisher exact test, as appropriate. Multivariable analysis was used to identify independent factors associated with SSI and SSO. RESULTS: Differences in American Society of Anesthesiologists class, body mass index, diabetes mellitus, chronic obstructive pulmonary disease, tobacco use, hernia type, prior abdominal surgery, prior ventral hernia repair, hernia size, and total infections were identified by grade. There was no difference in SSI or SSO by grade. Multivariable analysis revealed institution and number of prior abdominal operations to be associated with SSI. Institution, prostate disease, and prior ventral hernia repair were associated with SSO. CONCLUSIONS: The VHWG classification was unable to predict SSI and SSO and may not be applicable in LVHR. This study identified independent factors associated with SSI and SSO in LVHR. Although further study is warranted to validate these results, the factors presented may be a useful tool to stratify patient risk of SSI and SSO with LVHR.

Recurrence and pseudorecurrence after laparoscopic ventral hernia repair: predictors and patient-focused outcomes.

Laparoscopic ventral hernia repair (LVHR) is gaining popularity as an option to repair abdominal wall hernias. Bulging after repair remains common after this technique. This study evaluates the incidence and factors associated with bulging after LVHR. Between 2000 and 2010, 201 patients underwent LVHR at two affiliated institutions. Patients who developed recurrence or pseudorecurrence (seroma or eventration) were analyzed with univariate and multivariate analyses to identify predictors of these complications. Of the 201 patients who underwent LVHR, 40 (19.9%) patients developed a seroma, 63 (31.3%) patients had radiographically proven eventration, and 25 (12.4%) patients had a hernia recurrence. On multivariate analysis, seromas were associated with number of prior ventral hernia repairs, surgical site infections, and prostate disease. Mesh eventration was associated with hernia size and surgical technique. Tissue eventration was associated with primary hernias and surgical technique. Hernia recurrence was associated with incisional hernias and mesh type used. Recurrence and pseudorecurrence are important complications after LVHR. Large hernia size, infections, and surgical technique are important clinical factors that affect outcomes after LVHR.

Axillary artery cannulation in surgery for acute or subacute ascending aortic dissections.

BACKGROUND: Perfusion through the right axillary artery is an alternative to aortic or femoral artery cannulation during surgery for ascending aortic dissections. The results of this strategy, particularly beyond the immediate postoperative period, are not well described. METHODS: Eighty-three patients (median age, 58 years) with acute or subacute ascending aortic dissection underwent surgical repair with right axillary artery perfusion through an interposition Dacron graft. Sixty-five patients (78%) had DeBakey type I dissections. Procedures performed concomitantly with ascending aortic replacement included root replacement (n = 16; 19%), aortic valve repair or replacement (n = 51; 61%), and coronary artery bypass grafting (n = 13; 16%). Hypothermic circulatory arrest with antegrade cerebral perfusion was used in the majority of patients (n = 60; 72%). We retrospectively studied short-term and midterm outcomes, including survival and complications relating to the axillary cannulation. RESULTS: No patient incurred intraoperative axillary artery injuries or had arm ischemia. Fourteen patients (17%) died in the hospital or within 30 days of surgery, and 9 patients (11%) had strokes. Actuarial survival was 73% +/- 5% at 1 year and 64% +/- 6% at 3 years. Forty-six of the 57 surviving patients could be contacted by telephone; they reported few late complications related to the axillary artery cannulation site. These complications included 1 case each of right-arm weakness and right-arm numbness. CONCLUSIONS: Surgical repair of acute aortic dissection with right axillary artery perfusion can be performed safely, with a relatively low risk of stroke and a high probability of midterm survival.

Randomized comparison of cold blood and cold crystalloid renal perfusion for renal protection during thoracoabdominal aortic aneurysm repair.

OBJECTIVE: More effective adjuncts are needed to reduce the incidence of acute renal injury after thoracoabdominal aortic aneurysm (TAAA) repair. The purpose of this randomized trial was to determine whether renal perfusion with cold blood provides better protection against renal ischemia than perfusion with cold crystalloid in patients undergoing TAAA repair with left heart bypass. METHODS: One hundred seventy-two patients were enrolled. Strict inclusion criteria were used, including planned Crawford extent II or III TAAA repair with left heart bypass. The patients were randomly assigned to receive intermittent renal perfusion with either 4 degrees C lactated Ringer's solution (n = 86) or 4 degrees C blood (n = 86). Renal complications within 10 days of operation were stratified by renal dysfunction score (RDS). Postoperative changes in the levels of five urinary biomarkers-retinol binding protein, alpha-1 microglobulin, microalbumin, N-acetyl-beta-D-glucosaminidase, and intestinal alkaline phosphatase-were compared to assess potential differences in subclinical renal injury. RESULTS: Although total ischemic times were longer in the cold blood group, unprotected ischemic times were similar between the two groups. Twenty-seven patients in the cold blood group (31%) and 21 patients in the cold crystalloid group (24%) had peak RDS >or=2 (serum creatinine >50% above baseline; P = .4). There were no differences between the cold blood and cold crystalloid groups in the incidence of early death (7/86 [8%] vs 5/86 [6%], respectively; P = .8) or renal failure requiring hemodialysis (3/86 [3%] in both groups). Changes in renal biomarker levels were also similar in the two groups. Spinal cord deficits developed in 5 patients in the cold blood group (6%); there were no such deficits in the cold crystalloid group (P = .06). CONCLUSION: Cold renal perfusion during TAAA repair provides effective protection against renal injury. Using cold blood instead of cold crystalloid does not enhance renal protection.

Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan's syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan's syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease.

Delayed spinal cord deficits after thoracoabdominal aortic aneurysm repair.

BACKGROUND: Limited information is available about the treatment and outcomes of delayed paraplegia after thoracoabdominal aortic aneurysm (TAAA) repair. The objective of this study was to assess factors that precipitate and favorably affect delayed-onset neurologic deficits. METHODS: Over a 19-year period, 2,368 TAAA repairs were performed. Of the 93 patients (3.9%) who had postoperative paraplegia or paraparesis, 34 (37%) initially had intact neurologic function, but a delayed spinal cord deficit developed. We retrospectively examined clinical factors and events associated with development of the deficits, treatments used, and outcomes. Factors related to functional status were evaluated by comparing survivors who were ambulatory at discharge or transfer with those who were not. RESULTS: The delayed deficits occurred between 13 hours and 91 days postoperatively and were associated with a period of hypotension in 9 patients (26%). Two patients (6%) died in hospital. Of the 32 patients discharged or transferred, 13 (41%) were ambulatory. Poor functional outcomes were associated with female sex, intraoperative cerebrospinal fluid drainage, fewer intercostal arteries reattached, and administration of corticosteroids or osmotic diuretics. The actuarial survival rate at 2 years was 80% +/- 13% for the ambulatory patients and 32% +/- 12% for the nonambulatory patients (p = 0.002). CONCLUSIONS: Although precipitating episodes of hypoperfusion were common, most cases of delayed paraplegia occurred without such events, suggesting that other factors may play an important role in the development of this complication. Ambulatory status at discharge significantly predicts midterm survival.

Increased collagen deposition and elevated expression of connective tissue growth factor in human thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is characterized by dysregulated extracellular matrix. Little is known about the alterations of collagen and stimulators of collagen synthesis, eg, connective tissue growth factor (CTGF), in patients with TAD. In this study, we examined their roles in TAD. METHODS AND RESULTS: Surgical specimens of the aortic wall of TAD patients (n=10) and controls (n=10) were tested for collagen types I and III and CTGF expression. When compared with controls, protein levels of type I and III collagen and CTGF were significantly increased by 3.2-, 3.7-, and 5.3-fold, respectively (P<0.05 for all). Similar patterns were shown in mRNA levels of type Ialpha and Ialpha2 collagen and CTGF. Using immunohistochemistry and trichrome staining, we also observed elevated levels of collagen in the aortic media and adventitia. Treatment with recombinant human CTGF increased collagen synthesis in cultured aortic smooth muscle cells in a dose- and time-dependent fashion, in which expression of collagens increased from 506+/-108 counts per minute to 2764+/-240 cpm by 50 ng/mL CTGF, and from 30+/-43 cpm to 429+/-102 cpm at 48 hours. CONCLUSIONS: TAD patients exhibited significantly increased expression of aortic collagen types I and III as well as CTGF, which is likely to be responsible for the compromised aortic distensibility and systemic compliance. Because CTGF can increase collagen expression, CTGF may be a new target molecule in the pathogenesis and progression of TAD.

A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (-8202A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection.

OBJECTIVE: Matrix metalloproteinase 9 plays an important role in the maintenance of the aortic extracellular matrix. Genetic variations that affect protease expression or activity might contribute to thoracic aortic disease. The purpose of this study was to determine whether 3 single nucleotide polymorphisms in the matrix metalloproteinase 9 gene are associated with thoracic aortic aneurysms and dissection. METHODS: Genomic DNA was isolated from blood or aortic tissue from 28 patients with degenerative thoracic aortic aneurysms, 60 patients with thoracic aortic dissection, and 111 control patients. The frequency distributions of 3 matrix metalloproteinase 9 single nucleotide polymorphisms (-8202A/G, IVS4+3G/T, and 2003A/G [Q668R]) were determined by using genotyping accomplished with a real-time detection system. Associations between polymorphisms and disease were estimated with odds ratios and their 95% confidence intervals. RESULTS: The frequency of the -8202G allele was significantly higher in patients with thoracic aortic aneurysms and aortic dissection (0.52 and 0.56, respectively) than in control subjects (0.36, P < .001). Patients with thoracic aortic aneurysms or dissection were nearly 5 times more likely than control subjects to have the G allele (adjusted odds ratio, 4.87; 95% confidence interval, 2.04-11.64). There were no significant associations between the IVS4+3G/T or 2003A/G polymorphisms and thoracic aortic disease. CONCLUSIONS: The matrix metalloproteinase 9 -8202A/G polymorphism is associated with thoracic aortic aneurysms and dissection. Further studies are warranted to elucidate the functional role of the -8202A/G variant in matrix metalloproteinase 9 expression.

Spectrum of aortic operations in 300 patients with confirmed or suspected Marfan syndrome.

BACKGROUND: Cardiovascular disease is the main cause of morbidity and mortality in patients with Marfan syndrome. Many patients with presumed Marfan syndrome do not meet current diagnostic criteria. This study reviews the surgical aspects of aortic disease in 300 patients referred with the diagnosis of Marfan syndrome. METHODS: During a 16-year period, 300 patients with presumed Marfan syndrome underwent 398 operations on the aorta and branch arteries, including 125 aortic root operations, 59 aortic arch repairs, 31 descending thoracic aortic repairs, and 178 thoracoabdominal aortic repairs. Based on medical record review, patients were classified as confirmed Marfan syndrome if documented features satisfied current diagnostic criteria; patients not meeting these criteria were classified as suspected Marfan syndrome. RESULTS: There were 17 operative deaths (4.3%) after the 398 operations. Survival after the initial referral operation was 96.2% +/- 1.5% at 1 year, 82.7% +/- 2.4% at 5 years, and 74.6% +/- 3.1% at 10 years. Presentations, operative details, and outcomes were remarkably similar in the 137 patients (45.7%) with confirmed Marfan syndrome and the 163 patients (54.3%) with suspected Marfan syndrome. Freedom from repair failure, however, was significantly better in patients with confirmed Marfan syndrome (90.3% +/- 2.3% at 10 years) than in those with suspected Marfan syndrome (82.0% +/- 3.1% at 10 years; p = 0.001). CONCLUSIONS: Operative treatment of the full spectrum of aortic disease in Marfan patients enables excellent long-term survival. Similarities in surgical aspects of aortic disease suggest that patients with features of Marfan syndrome who do not meet diagnostic criteria should be managed in the same manner as patients with confirmed Marfan syndrome.

The elephant trunk technique for staged repair of complex aneurysms of the entire thoracic aorta.

BACKGROUND: Extensive thoracic aortic aneurysms that involve the ascending, arch, and descending segments require challenging repairs associated with substantial morbidity and mortality. The purpose of this report is to evaluate contemporary outcomes after surgical repair of extensive thoracic aortic aneurysms using a two-stage approach with the elephant trunk technique. METHODS: During a 15 1/2-year period, 148 consecutive patients underwent total aortic arch replacement using the elephant trunk technique. Seventy-six of these patients (51%, 76/148) returned for second-stage repair of the descending thoracic or thoracoabdominal aorta 4.9 +/- 7.5 months after the first stage. RESULTS: Operative mortality after the proximal aortic stage was 12% (18/148). Seven patients (5%) had strokes. Among the patients who subsequently underwent distal aortic repair, operative mortality was 4% (3/76). Two patients (3%) developed paraplegia. Long-term survival after completing the second stage of repair was 70 +/- 6% at 5 years and 59 +/- 7% at 8 years. CONCLUSIONS: Contemporary management of extensive thoracic aortic aneurysms using the two-stage elephant trunk technique yields acceptable short-term and long-term outcomes. This technique remains an important component of the surgical armamentarium.

The reversed elephant trunk technique used for treatment of complex aneurysms of the entire thoracic aorta.

OBJECTIVE: A preferred technique for the staged treatment of patients with aneurysms involving the entire thoracic aorta is the elephant trunk technique, with replacement of the proximal (ascending and transverse aortic arch) aorta as the initial procedure. Some patients, however, need to have the distal aortic segments (descending and thoracoabdominal aorta) addressed during the first operation. We evaluated outcomes in a series of patients who underwent distal aortic replacement first using the reversed elephant trunk technique. METHODS: Thirty-eight patients underwent first-stage graft repair of the descending thoracic (n = 3) or thoracoabdominal (n = 35) aorta using the reversed elephant trunk technique. Twelve patients (32%) ultimately underwent second-stage aortic arch replacement after a mean interval of 3.9 months (range, 1.6-14 months). RESULTS: The operative mortality for the initial procedure was 16% (6/38 patients). One patient had a stroke (3%) and 1 patient developed paraparesis (3%). In the interval between the 2 procedures, there were 4 late deaths (4/32; 13%), 1 due to respiratory failure and 3 due to unknown causes. After the 12 completion procedures, there was 1 in-hospital death (8%) and there were no strokes. Five-year survival for the overall group was 51.3 +/- 10.8%. CONCLUSIONS: Surgical treatment of aneurysms involving the entire thoracic aorta remains challenging and is associated with substantial morbidity and mortality. The reversed elephant trunk technique facilitates staged repair in patients who require distal aortic replacement during the first operation.

Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection.

BACKGROUND: Thoracic aortic aneurysmal diseases are characterized by degeneration of elastin within the aortic wall. Although proteinases, such as matrix metalloproteinase, appear to contribute to elastin degradation, little is known about the role of elastic fiber assembly in such diseases. Fibulin-5 is an extracellular protein that is expressed in the vascular basement membrane and regulates elastic fiber assembly by microfibril machinery. In this study, we examined whether thoracic aortic dissection (TAD) is associated with abnormal fibulin-5 expression. METHODS: Intraoperative aortic samples were obtained from 21 patients with proximal aortic dissection. Control aortic tissue was obtained from 11 organ donors, heart transplant recipients, and patients undergoing coronary artery bypass. An in vitro culture of vascular smooth muscle cells was obtained from 2 TAD patients and 1 control subject. To evaluate elastin expression, we stained tissue sections with Verhoeff-Van Gieson stain. Fibulin-5 messenger RNA (mRNA) expression was determined by quantitative real-time reverse-transcriptase-polymerase chain reaction. RESULTS: Aortic fibulin-5 mRNA and elastin content were decreased in TAD patients, compared with controls (P=.001 and P=.02, respectively). Decreased fibulin-5 expression strongly correlated with decreased amounts and fragmentation of elastin in aortic samples from patients with TAD (r=0.83, P < .0001 and F=20.7, P < .0001 respectively). The fibulin-5 mRNA in aortic vascular smooth muscle cells collected from TAD demonstrated a 38% decrease in expression, compared with the control. CONCLUSIONS: Patients with proximal aortic dissection exhibited significantly decreased expression of aortic fibulin-5. Decreased fibulin-5 may contribute to the pathogenesis of aortic dissection by impairing elastic fiber assembly.

The threat of adhesive embolization: BioGlue leaks through needle holes in aortic tissue and prosthetic grafts.

BACKGROUND: BioGlue Surgical Adhesive (CryoLife, Inc, Kennesaw, GA) is used to reinforce anastomoses during cardiovascular operations. Previous reports have raised concerns that adhesives may leak through suture-line needle holes and that resulting intraluminal glue may embolize. The purpose of this study was to determine if BioGlue leaks through anastomotic needle holes in aortic tissue and two common prosthetic graft materials. METHODS: Polypropylene suture was used to create end-to-end anastomoses in gelatin-sealed woven polyester grafts (n = 45), expanded polytetrafluoroethylene (ePTFE) grafts (n = 45), and fresh porcine aortas (n = 45). An additional 45 anastomoses were created in ePTFE grafts using ePTFE sutures. The outer surface of each anastomosis was covered with BioGlue. Anastomoses underwent inspection with direct magnification or histology. RESULTS: BioGlue leaked through needle holes and into the lumen in 10% of anastomoses (18 of 180). Leaks were significantly more common in fresh aorta (10 of 45, 22%) than in prosthetic grafts (8 of 135, 6%; p = 0.003). Suture size did not significantly affect the incidence of leak. The use of ePTFE sutures did not eliminate BioGlue leakage. Prosthetic graft leaks created discreet round adhesive particles. In contrast, aortic tissue leaks resulted in thin, friable flakes of glue extending along the intimal surface. Aortic histology confirmed that BioGlue reached the vessel lumen via the suture channels. CONCLUSIONS: BioGlue leaked through the needle holes in fresh aortic tissue and prosthetic grafts. Intraluminal adhesive particles were easily dislodged, supporting concerns regarding embolization. The potential for adhesive embolization should be a factor when considering the relative risks and benefits of using BioGlue.

Organ protection during thoracoabdominal aortic surgery: rationale for a multimodality approach.

Surgical repair of thoracoabdominal aortic aneurysms (TAAAs) remains a technically challenging operation that requires a systematic approach to prevent ischemic complications and achieve excellent clinical outcomes. Techniques for organ protection have evolved substantially over the past 20 years. This review describes our current multimodality approach to organ protection during TAAA repair.

Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves.

BACKGROUND: Abnormal matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression contributes to the development of abdominal aortic aneurysms. Recent data suggest that MMP-2 and MMP-9 may also play a role in thoracic aortic disease. We sought to determine (1) whether ascending aortic aneurysms are associated with increased MMP expression and (2) whether aortic inflammation and MMP expression differ between patients with congenital bicuspid aortic valves (BAVs) and those with trileaflet aortic valves (TAVs). MATERIALS AND METHODS: Samples of ascending aortic aneurysms were obtained from 29 patients; 14 patients had BAVs and 15 had TAVs. Control ascending aorta was obtained from 14 organ donors or heart transplant recipients. Aortic histology and immunohistochemistry were performed to evaluate elastin degradation, inflammatory changes, and MMP-2 and MMP-9 expression. Aortic levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured using ELISA. RESULTS: Aneurysms in the TAV patients exhibited marked inflammation, high CD68 expression, diminished elastin content, increased MMP-9 expression, and normal MMP-2 levels. In contrast, BAV aneurysms were characterized by a relative lack of inflammation, preservation of elastin content, normal MMP-9 levels, and elevated MMP-2 expression. TIMP-1 and TIMP-2 levels were not significantly different among the three groups. CONCLUSIONS: Ascending aortic aneurysms exhibited increased MMP expression. The pattern of MMP expression and the degree of inflammation, however, differed between aneurysms associated with BAVs and those with TAVs. Variations in the molecular mechanisms underlying different types of thoracic aortic aneurysms warrant further investigation.